Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA267570 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Effect of DMF and MEF on gene expression in select mouse organs: Multi-dosing regimen
| PRJNA267571 | ENA
Project description:Effect of DMF and MEF on gene expression in select mouse organs
| PRJNA267567 | ENA
Project description:Delayed-release dimethyl fumarate (DMF) is approved in the United States, European Union, Canada, and Australia for the treatment of multiple sclerosis. DMF is also a component in a defined-mixture product with three salts of monoethyl fumarate (MEF) that is approved in Germany for the treatment of psoriasis. Characterizing common or distinct pharmacodynamic properties of DMF and MEF would provide insights into the mechanisms of action of delayed-release DMF versus fixed combination products containing DMF and MEF salts. In this study we evaluated the pharmacodynamic effects and pharmacokinetics of DMF and MEF in central nervous system and peripheral tissues of naïve mice following a single dose or 10 daily doses of DMF, MEF, or a combination of the two. DMF and MEF exhibited similar pharmacokinetic profiles, but differences were noted in biodistribution: monomethyl fumarate (MMF, the primary metabolite of DMF) exhibited a higher degree of brain penetration, whereas MEF was preferentially partitioned into kidney. Both common and distinct pharmacodynamic responses were observed in all assessed tissues for DMF and MEF alone or in combination. These findings indicate that all fumaric acid esters cannot be considered equivalent, and combinations of compounds may exert effects not observed when agents are used individually.
2020-12-10 | GSE63343 | GEO
Project description:Delayed-release dimethyl fumarate (DMF) is approved in the United States, European Union, Canada, and Australia for the treatment of multiple sclerosis. DMF is also a component in a defined-mixture product with three salts of monoethyl fumarate (MEF) that is approved in Germany for the treatment of psoriasis. Characterizing common or distinct pharmacodynamic properties of DMF and MEF would provide insights into the mechanisms of action of delayed-release DMF versus fixed combination products containing DMF and MEF salts. In this study we evaluated the pharmacodynamic effects and pharmacokinetics of DMF and MEF in central nervous system and peripheral tissues of naïve mice following a single dose or 10 daily doses of DMF, MEF, or a combination of the two. DMF and MEF exhibited similar pharmacokinetic profiles, but differences were noted in biodistribution: monomethyl fumarate (MMF, the primary metabolite of DMF) exhibited a higher degree of brain penetration, whereas MEF was preferentially partitioned into kidney. Both common and distinct pharmacodynamic responses were observed in all assessed tissues for DMF and MEF alone or in combination. These findings indicate that all fumaric acid esters cannot be considered equivalent, and combinations of compounds may exert effects not observed when agents are used individually.
2020-12-10 | GSE63361 | GEO
Project description:Chronic graft-versus-host disease (cGVHD), characterized by chronic tissue inflammation and fibrosis involving multiple organs, remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF) is an anti-inflammatory drug approved for the treatment of multiple sclerosis and psoriasis. We previously reported that DMF effectively inhibits acute GVHD (aGVHD) while preserving the graft-versus-leukemia effect. However, the role of DMF in cGVHD progression remains unknown. Here, we found that DMF administration significantly suppresses follicular helper T cell (Tfh) differentiation, germinal center formation and alleviates disease severity in different murine cGVHD models. Mechanistically, DMF treatment downregulates IL-21 transcription by activation of Nrf2, thus orchestrating Tfh-related gene program both in mice and humans. The inhibitory role of DMF on Tfh cell differentiation was diminished in Nrf2 deficient T cells. Importantly, the therapeutic potential of DMF in clinical cGVHD has been validated in human data whereby DMF effectively reduces IL-21 production and Tfh cell generation in peripheral blood mononuclear cells from active cGVHD patients and further attenuates xenograft GVHD. Collectively, our findings reveal that DMF potently inhibits cGVHD development by repressing Tfh cell differentiation via Nrf2, paving way for the treatment of cGVHD in the clinic.
2024-12-02 | GSE269610 | GEO
Project description:We report label-free and targeted quantification of xenobiotic metabolizing enzymes (XME) and transporters in 39 human liver microsomal samples. More than 2800 proteins were identified and quantified. These data can be used in physiologically based pharmacokinetic models for dosage regimen design and precision dosing.
2021-09-09 | PXD021025 | Pride
Project description:A quantitative phosphoproteomic study was performed on mouse embryonic fibroblasts (MEF) knocked-out of IRE1 protein and re rexpressin it culturen in 25mM glucose media. The chosen experimental strategy was to perform phosphopeptide enrichment associated with multiplex protein identification and quantification by LC-MSMS on a high-resolution mass spectrometer using tandem mass tag (TMT9; Thermo Fisher Scientific) technology and High- Select Fe-NTA Phosphopeptide Enrichment Kit (Thermo Fisher Scientific).
2023-12-08 | PXD046579 | Pride
Project description:Dimethyl fumarate (DMF) is an immunomodulatory drug approved for the therapy of multiple sclerosis (MS). The identification of response biomarkers to DMF is a necessity in the clinical practice. With this aim, we studied the transcriptomic changes produced by DMF in peripheral blood mononuclear cells (PBMCs) and its association with clinical response. DMF induced a mild transcriptional effect, with only 328 differentially expressed genes (DEGs) after 12 months of treatment. The overall effect was a downregulation of pro-inflammatory genes, chemokines, and activators of the NF-kB pathway. At baseline, no DEGs were found between responders and non-responders. During DMF treatment a differential transcriptomic response was observed, with responders presenting a higher number of DEGs (902 genes) compared to non-responders (189 genes). Responder patients to DMF exhibit a distinguishable transcriptomic response compared to non-responders that should be further studied for the validation of biomarkers of treatment response to DMF.
2023-08-08 | GSE235357 | GEO
Project description:We generated Oct4 libraries by randomizing selected amino acids and by recombining domains of paralogous POU family genes. These libraries were subjected to iterative rounds of pooled screens to select variants that enhance pluripotency induction. We identified an artificially evolved POU factor (ePOU) that substantially outperforms wild-type Oct4 in terms of mouse embryonic fibrobast (MEF) reprogramming. To probe whether the ePOU and Oct4 differentially engage the chromatin of reprogramming cells, we performed chromatin immunoprecipitation sequencing (ChIPseq) for both factors and Sox2. Two cocktails Oct4 (O), Sox2 (S), Klf4 (K), c-Myc (M) and ePOU/S/K/M were transduced into OG2 MEF cells which is MEF cells with Oct4 promotor.
2021-02-07 | GSE104220 | GEO
Project description:Circulating Tumor Cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. Using a pancreatic cancer mouse model, we applied a microfluidic device to isolate CTCs independently of tumor epitopes, subjecting these to single cell RNA-sequencing. This study was conducted to determine the heterogeneity of pancreatic CTCs and to compare these CTCs to matched primary tumors, cell line controls (NB508 cancer cell line and MEF non-cancer cell line), primary tumor single cells, and normal leukocytes/WBCs.
2014-09-22 | GSE51372 | GEO